- EMDB-14547: Structure of CRL7FBXW8 reveals coupling with CUL1-RBX1/ROC1 for m... -
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Entry
Database: EMDB / ID: EMD-14547
Title
Structure of CRL7FBXW8 reveals coupling with CUL1-RBX1/ROC1 for multi-cullin-RING E3-catalyzed ubiquitin ligation
Map data
Sample
Complex: Structure of the CUL7-RBX1-FBXW8-SKP1 cullin-RING ligase complex
Protein or peptide: Cullin-7
Protein or peptide: F-box/WD repeat-containing protein 8
Protein or peptide: E3 ubiquitin-protein ligase RBX1
Protein or peptide: S-phase kinase-associated protein 1
Ligand: ZINC ION
Function / homology
Function and homology information
: / 3M complex / spongiotrophoblast layer development / F-box domain binding / anaphase-promoting complex / PcG protein complex / cullin-RING-type E3 NEDD8 transferase / XBP1(S) activates chaperone genes / cellular response to chemical stress / NEDD8 transferase activity ...: / 3M complex / spongiotrophoblast layer development / F-box domain binding / anaphase-promoting complex / PcG protein complex / cullin-RING-type E3 NEDD8 transferase / XBP1(S) activates chaperone genes / cellular response to chemical stress / NEDD8 transferase activity / cullin-RING ubiquitin ligase complex / Cul7-RING ubiquitin ligase complex / ubiquitin-dependent protein catabolic process via the C-end degron rule pathway / positive regulation of ubiquitin protein ligase activity / Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling / maintenance of protein location in nucleus / positive regulation of protein autoubiquitination / protein neddylation / NEDD8 ligase activity / positive regulation of dendrite morphogenesis / Cul5-RING ubiquitin ligase complex / negative regulation of response to oxidative stress / ubiquitin-ubiquitin ligase activity / labyrinthine layer blood vessel development / Cul4A-RING E3 ubiquitin ligase complex / SCF ubiquitin ligase complex / Cul2-RING ubiquitin ligase complex / negative regulation of type I interferon production / Cul4B-RING E3 ubiquitin ligase complex / ubiquitin ligase complex scaffold activity / regulation of mitotic nuclear division / SCF-dependent proteasomal ubiquitin-dependent protein catabolic process / Cul3-RING ubiquitin ligase complex / Prolactin receptor signaling / protein monoubiquitination / Golgi organization / cullin family protein binding / ubiquitin-like ligase-substrate adaptor activity / mitotic cytokinesis / epithelial to mesenchymal transition / vasculogenesis / protein K48-linked ubiquitination / Nuclear events stimulated by ALK signaling in cancer / positive regulation of TORC1 signaling / T cell activation / Regulation of BACH1 activity / MAP3K8 (TPL2)-dependent MAPK1/3 activation / post-translational protein modification / SCF-beta-TrCP mediated degradation of Emi1 / NIK-->noncanonical NF-kB signaling / molecular function activator activity / Vpu mediated degradation of CD4 / Degradation of DVL / Dectin-1 mediated noncanonical NF-kB signaling / Recognition of DNA damage by PCNA-containing replication complex / Degradation of GLI1 by the proteasome / Activation of NF-kappaB in B cells / Negative regulation of NOTCH4 signaling / cellular response to amino acid stimulus / Iron uptake and transport / GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2 / Vif-mediated degradation of APOBEC3G / Hedgehog 'on' state / DNA Damage Recognition in GG-NER / Degradation of GLI2 by the proteasome / GLI3 is processed to GLI3R by the proteasome / FBXL7 down-regulates AURKA during mitotic entry and in early mitosis / RING-type E3 ubiquitin transferase / Degradation of beta-catenin by the destruction complex / negative regulation of canonical Wnt signaling pathway / placenta development / Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha / Dual Incision in GG-NER / Evasion by RSV of host interferon responses / NOTCH1 Intracellular Domain Regulates Transcription / Transcription-Coupled Nucleotide Excision Repair (TC-NER) / Formation of TC-NER Pre-Incision Complex / CLEC7A (Dectin-1) signaling / beta-catenin binding / SCF(Skp2)-mediated degradation of p27/p21 / Regulation of expression of SLITs and ROBOs / Constitutive Signaling by NOTCH1 PEST Domain Mutants / Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants / Formation of Incision Complex in GG-NER / FCERI mediated NF-kB activation / microtubule cytoskeleton organization / Interleukin-1 signaling / Orc1 removal from chromatin / Dual incision in TC-NER / Gap-filling DNA repair synthesis and ligation in TC-NER / Regulation of RAS by GAPs / protein polyubiquitination / positive regulation of protein catabolic process / Regulation of RUNX2 expression and activity / Cyclin D associated events in G1 / cellular response to UV / Regulation of PLK1 Activity at G2/M Transition / KEAP1-NFE2L2 pathway / MAPK cascade / ubiquitin protein ligase activity Similarity search - Function
Journal: Nat Struct Mol Biol / Year: 2022 Title: Structure of CRL7 reveals coupling with CUL1-RBX1/ROC1 for multi-cullin-RING E3-catalyzed ubiquitin ligation. Authors: Linus V M Hopf / Kheewoong Baek / Maren Klügel / Susanne von Gronau / Yue Xiong / Brenda A Schulman / Abstract: Most cullin-RING ubiquitin ligases (CRLs) form homologous assemblies between a neddylated cullin-RING catalytic module and a variable substrate-binding receptor (for example, an F-box protein). ...Most cullin-RING ubiquitin ligases (CRLs) form homologous assemblies between a neddylated cullin-RING catalytic module and a variable substrate-binding receptor (for example, an F-box protein). However, the vertebrate-specific CRL7 is of interest because it eludes existing models, yet its constituent cullin CUL7 and F-box protein FBXW8 are essential for development, and CUL7 mutations cause 3M syndrome. In this study, cryo-EM and biochemical analyses reveal the CRL7 assembly. CUL7's exclusivity for FBXW8 among all F-box proteins is explained by its unique F-box-independent binding mode. In CRL7, the RBX1 (also known as ROC1) RING domain is constrained in an orientation incompatible with binding E2~NEDD8 or E2~ubiquitin intermediates. Accordingly, purified recombinant CRL7 lacks auto-neddylation and ubiquitination activities. Instead, our data indicate that CRL7 serves as a substrate receptor linked via SKP1-FBXW8 to a neddylated CUL1-RBX1 catalytic module mediating ubiquitination. The structure reveals a distinctive CRL-CRL partnership, and provides a framework for understanding CUL7 assemblies safeguarding human health.
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